机构：[1]Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.[4]Tianfu Jincheng Laboratory, Chengdu 610041, Sichuan, China.[5]Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu 611130, Sichuan, China.
Neurodegenerative diseases (NDs) are currently incurable diseases that cause progressive degeneration of nerve cells. Many of the disease-causing proteins of NDs are "undruggable" for traditional small-molecule inhibitors (SMIs). None of the compounds that attenuated the amyloid-β (Aβ) accumulation process have entered clinical practice, and many phase III clinical trials of SMIs for Alzheimer's disease (AD) have failed. In recent years, emerging targeted protein degradation (TPD) technologies such as proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimaeras (LYTACs), and autophagy-targeting chimeras (AUTACs) with TPD-assistive technologies such as click-formed proteolysis-targeting chimeras (CLIPTACs) and deubiquitinase-targeting chimera (DUBTAC) have developed rapidly. In vitro and in vivo experiments have also confirmed that TPD technology can target the degradation of ND pathogenic proteins, bringing hope for the treatment of NDs. Herein, we review the latest TPD technologies, introduce their targets and technical characteristics, and discuss the emerging TPD technologies with potential in ND research, with the hope of providing a new perspective for the development of TPD technology in the NDs field.
基金：
This work was supported by the National Natural Science
Foundation of China (81903502, 82073318), the Sichuan
Science and Technology Program (2019YFS0003), the
National Major Scientific and Technological Special Project
for Significant New Drugs Development (2018ZX09201018-
021), the Natural Science Foundation of Sichuan Province
(2022NSFSC1365), the 1.3.5 project for disciplines of
excellence, West China Hospital, Sichuan University
(ZYGD20001), the Nonprofit Central Research Institute
Fund of the Chinese Academy of Medical Sciences (2020-
JKCS-014), the Health Commission of Sichuan Province
(21PJ149), and the Xinglin Foundation of Chengdu University
of TCM (YYZX2021043).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区药物化学
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.[2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.[2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.[4]Tianfu Jincheng Laboratory, Chengdu 610041, Sichuan, China.[*1]Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China[*2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China[*3]Tianfu Jincheng Laboratory, Chengdu 610041 Sichuan, China
推荐引用方式(GB/T 7714)：
Fang Yingxu,Wang Jiaxing,Zhao Min,et al.Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy[J].Journal of medicinal chemistry.2022,doi:10.1021/acs.jmedchem.2c00844.
APA：
Fang Yingxu,Wang Jiaxing,Zhao Min,Zheng Qinwen,Ren Changyu...&Zhang Jifa.(2022).Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy.Journal of medicinal chemistry,,
MLA：
Fang Yingxu,et al."Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy".Journal of medicinal chemistry .(2022)
医学